Programm                 "Degeneration und Regeneration– Grundlagen, Diagnostik und Therapie"


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Abstract
Abstract

bFGF-Induced Proliferation of Müller Glial Cells: Dependence on Transactivation of EGF and PDGF Receptor Tyrosine Kinases

Hollborn M., Jahn K., Bringmann A., Wiedemann P., Kohen L.
University of Leipzig, Eye Hospital

Purpose: The basic fibroblast growth factor (bFGF) plays a central role in the mediation of responses of the sensory retina to pathogenic events and is one of the main growth factors which stimulates the proliferation of retinal cells in proliferative retinopathies. By using cells of an immortalized human Müller cell line (MIO-M1), we investigated whether the proliferation-stimulating effect of bFGF is mediated by transactivation of other receptor tyrosine kinases and by activation of mitogen-activated protein kinases (MAPKs).
Method: The proliferation rate of the cultured cells was determined by a bromodeoxyuridine (BrdU) incorporation assay. The activation of different receptor tyrosine kinases was analyzed with specific inhibitors. In order to determine whether the cultured cells are stimulated via autocrine secretion of growth factors, antibodies against PDGF, EGF, and HB-EGF were applied.
Results: The proliferation of human Müller cells in vitro was stimulated by bFGF in a dose-dependent manner. The mitogenic effect of bFGF was blocked in the presence of inhibitors of the PDGF- or the EGF receptor tyrosine kinases. An extracellular stimulation of the cell proliferation by autocrine release of PDGF, EGF, or of HB-EGF could be excluded. Similarly, a broad-spectrum inhibitor of matrix metalloproteinases was without effect. The bFGF-induced prolifera


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